下颚骨形成过程中金属蛋白酶的表达动态:与Myb转录因子的关联。
Expression dynamics of metalloproteinases during mandibular bone formation: association with Myb transcription factor.
发表日期:2023
作者:
S Varadinkova, V Oralova, M Clarke, J Frampton, L Knopfova, H Lesot, P Bartos, E Matalova
来源:
Frontiers in Cell and Developmental Biology
摘要:
在牙齿形成并变得功能正常的过程中,牙槽骨被重塑。已知金属蛋白酶在这一过程中起到了一定的作用,但是新的调控因子正在出现,其环境适应性也引发了挑战。这适用于Myb,最近被报道参与了骨骼发育和再生的转录因子。Myb对Mmps表达的调控效应主要在肿瘤发生中进行了研究,在这种情况下,Myb影响了Mmp1、Mmp2、Mmp7和Mmp9的表达。本研究的目的是评估Myb对Mmps基因表达的调控影响,对骨发育和下颌骨形成产生影响。为此,使用了敲除小鼠模型。分析了Myb敲除小鼠下颌骨在存活极限处的与骨相关的Mmps基因表达以及关键的成骨转录因子Runx2和Sp7的基因表达。在研究中的金属蛋白酶中,Mmp13显着下调。通过在头盖骨来源的细胞中过表达Myb,进一步确认了Myb对Mmp13的表达的影响,从而导致Mmp13的上调。在下颌骨/牙槽骨发育过程中,同时观察了Mmp13与其他Mmps的表达,以及Myb、Sp7和Runx2的表达。最显著的变化观察在Mmp9和Mmp13的表达中。这些MMPs和MYB的定位也通过免疫组织化学方法进行,发现它们存在于前/成骨细胞以及前/成骨细胞中。总之,这些结果提供了关于下颌骨/牙槽骨形成过程中与骨发生相关的Mmps表达动态的全面了解,并指出Myb可能是Mmp13的另一个潜在调节因子。
Copyright © 2023 Varadinkova, Oralova, Clarke, Frampton, Knopfova, Lesot, Bartos and Matalova.
As the dentition forms and becomes functional, the alveolar bone is remodelled. Metalloproteinases are known to contribute to this process, but new regulators are emerging and their contextualization is challenging. This applies to Myb, a transcription factor recently reported to be involved in bone development and regeneration. The regulatory effect of Myb on Mmps expression has mostly been investigated in tumorigenesis, where Myb impacted the expression of Mmp1, Mmp2, Mmp7, and Mmp9. The aim of this investigation was to evaluate the regulatory influence of the Myb on Mmps gene expression, impacting osteogenesis and mandibular bone formation. For that purpose, knock-out mouse model was used. Gene expression of bone-related Mmps and the key osteoblastic transcription factors Runx2 and Sp7 was analysed in Myb knock-out mice mandibles at the survival limit. Out of the metalloproteinases under study, Mmp13 was significantly downregulated. The impact of Myb on the expression of Mmp13 was confirmed by the overexpression of Myb in calvarial-derived cells causing upregulation of Mmp13. Expression of Mmp13 in the context of other Mmps during mandibular/alveolar bone development was followed in vivo along with Myb, Sp7 and Runx2. The most significant changes were observed in the expression of Mmp9 and Mmp13. These MMPs and MYB were further localized in situ by immunohistochemistry and were identified in pre/osteoblastic cells as well as in pre/osteocytes. In conclusion, these results provide a comprehensive insight into the expression dynamics of bone related Mmps during mandibular/alveolar bone formation and point to Myb as another potential regulator of Mmp13.Copyright © 2023 Varadinkova, Oralova, Clarke, Frampton, Knopfova, Lesot, Bartos and Matalova.